title: The role of death-associated protein kinase (DAPK) in endothelial apoptosis under fluid shear stress.
abstract: Endothelial cells are the interface between hemodynamic fluid flow and vascular tissue contact. They actively translate physical and chemical stimuli into intracellular signaling cascades which in turn regulate cell function, and endothelial dysfunction leads to inflammation and diseased conditions. For example, atherosclerosis, a chronic vascular disease, favorably develops in regions of disturbed fluid flow and low shear stress. Apoptosis, or programmed cell death, must be properly regulated to maintain homeostasis in the vascular wall. The loss of apoptosis control, as seen in low shear stress regions, is implicated in various diseases such as atherosclerosis and cancer. Death-associated protein kinase (DAPK) is a pro-apoptotic regulator for various cell types that is localized in the cell cytoskeleton and regulates changes in cytoplasm associated with apoptosis. Yet its role in endothelial cells remains unclear. Laminar shear stress inhibits cytokine, oxidative stress, and serum starvation induced endothelial apoptosis, while extended shearing elicit structural changes and cell alignment. We hypothesize that DAPK potentially plays a role in attenuating endothelial apoptosis in response to shear stress. We found that shear stress regulates DAPK expression and apoptotic activity in endothelial cells. In fact, shear stress alone induces DAPK and apoptosis, but has the opposite effect in the presence of apoptotic triggers such as tissue necrosis factor α (TNFα). This review summarizes mechanisms of endothelial mechanotransduction and apoptosis, and explores the potential of DAPK as a novel signaling pathway involved in mediating protective effects of shear stress on the vasculature.
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN 46202, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Rennier
authors.forename: Julie Y
authors.initials: JY
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D050197:Atherosclerosis / Q000201:enzymology / Q000473:pathology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D064550:Death-Associated Protein Kinases; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D033081:Shear Strength / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D051017:Apoptosis Regulatory Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases
keywords: Apoptosis; Atherosclerosis; DAPK; Endothelial cells; Shear stress